Bendamustine in combination with rituximab for elderly patients with previously untreated B-cell chronic lymphocytic leukemia: A retrospective analysis of real-life practice in Italian hematology departments

Laurenti, Luca; Innocenti, Idanna; Autore, Francesco; Vannata, Barbara; Efremov, Dimitar G.; Ciolli, Stefania; Poeta, Giovanni Del; Mauro, Francesca Romana; Cortelezzi, Agostino; Borza, Paola Anticoli; Ghio, Francesco; Mondello, Patrizia; Murru, Roberta; Gozzetti, Alessandro; Cariccio, Maria Rosa Lanza; Piccirillo, Nicola; Boncompagni, Riccardo; Cantonetti, Maria; Principe, Maria Ilaria Del; Reda, Gianluigi; Bongarzoni, Velia; Cervetti, Giulia; Pitini, Vincenzo; Foà, Robin; Sica, Simona; D’Arena, Giovanni

doi:10.1016/j.leukres.2015.07.009

Cited by 31 publications

(24 citation statements)

References 21 publications

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“…The frequencies of hematologic AEs in this study were generally similar to those in previously published reports of CLL treatments, but the frequencies of nonhematologic AEs were generally higher than those in other published studies involving chemoimmunotherapy regimens . The finding that the mean monthly per‐patient costs increased gradually with the number of unique AEs highlights the substantial economic burden associated with toxicities.…”

Section: Discussionsupporting

confidence: 85%

Treatment patterns, adverse events, and economic burden in a privately insured population of patients with chronic lymphocytic leukemia in the United States

Kabadi

Nagar

et al. 2019

Cancer Medicine

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Introduction Contemporary data describing treatment patterns, adverse events (AEs), and outcomes in patients with chronic lymphocytic leukemia (CLL) in clinical practice are lacking. We conducted a retrospective cohort study and assessed treatment patterns, AEs, health‐care resource use (HCRU), and costs in patients with diagnosis of CLL. Methods Using a nationally representative population of privately insured patients in the US, adult patients with CLL diagnosis (July 2012‐June 2015) were selected if they had continuous health plan enrollment for ≥12 months before the first CLL diagnosis without any evidence of any CLL‐directed treatment. Treatment patterns up to four lines of therapy (LOT) and occurrence of AEs during CLL therapies were assessed. Mean per‐patient monthly HCRU and costs were assessed overall and by number of unique AEs. Results Of all patients meeting the selection criteria (n = 7,639; median age, 66 years), 18% (n = 1,379) received a systemic therapy during study follow‐up. Of these, bendamustine/rituximab (BR) was the most common first observed regimen (28.1%), while ibrutinib was the most common therapy in the second (20.8%) and third (25.5%) observed regimens. The mean monthly all‐cause and CLL‐related costs, among patients treated with a systemic therapy, were $7,943 (SD = $15,757) and $5,185 (SD = $9,935), respectively. Mean monthly all‐cause costs increased by the number of AEs (from $905 [SD = $1,865] among those with no AEs to $6,032 [SD = $13,290] among those with ≥6 AEs). Conclusions Chemoimmunotherapy, particularly BR, was the most common first observed therapy for CLL, whereas ibrutinib was most preferred in the second and third observed lines of therapy during the study period. Findings demonstrate that the economic burden of AEs in CLL is substantial.

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Section: Discussionsupporting

confidence: 85%

Treatment patterns, adverse events, and economic burden in a privately insured population of patients with chronic lymphocytic leukemia in the United States

Kabadi

Nagar

et al. 2019

Cancer Medicine

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“…The responses were significantly higher in the patients treated with chlorambucil and ofatumumab (ORR 82% vs 69%, CR 14% vs. 1%, median PFS 22 vs. 13 months). A recently reported phase II study of combination initial therapy for 70 elderly patients (median age 72 years) with CLL using bendamustine and rituximab achieved a ORR of 89% with 31% CR and median PFS of 79% at 2 years [30]. The mAb combination therapy used in our trial achieved an ORR and CR comparable to these chemoimmunotherapy regimens but with a shorter PFS.…”

Section: Discussionmentioning

confidence: 68%

A phase II randomized trial comparing standard and low dose rituximab combined with alemtuzumab as initial treatment of progressive chronic lymphocytic leukemia in older patients: a trial of the ECOG‐ACRIN cancer research group (E1908)

et al. 2016

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Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) patients requiring initial therapy are often older and frailer and unsuitable candidates for standard chemoimmunotherapy regimens. Shorter duration combination monoclonal antibody (mAb) therapy using alemtuzumab and rituximab has been shown to be effective and tolerable treatment for CLL. Standard dose anti-CD20 mAb therapy causes loss of CD20 expression by surviving CLL cells, which can be minimized by decreasing the mAb dose. We report a randomized phase II clinical trial enrolling older (≥65 years) patients (median age 76 years, n=31) with treatment naïve progressive CLL. Patients received 8–12 weeks of standard subcutaneous alemtuzumab with either intravenous standard (375 mg/m2 weekly)(n=16) or low dose (20 mg/m2 3x week)(n=15) rituximab. This study was closed before full accrual because the manufacturer withdrew alemtuzumab for treatment of CLL. The overall response rate was 90% with an 45% complete response rate, median progression free survival of 17.9 months and no significant differences in outcome between the low and standard dose rituximab arms. The major toxicities were cytopenia and infection with one treatment fatality caused by progressive multifocal leukoencephalopathy but no other opportunistic infections. Combination mAb therapy was effective and tolerable treatment for older and frailer patients with progressive CLL, achieving a high rate of complete remissions. These data support the role of mAb in therapy for less fit CLL patients and the further study of low dose higher frequency anti-CD20 mAb therapy as a potentially more effective use of anti-CD20 mAb in the treatment of CLL.

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“…2 We found the reduction of TRM in BFR-treated patients to be less than that in FCR-treated patients among low-risk (0% vs. 19%, respectively) and high-risk (14% vs. 28%, respectively) CLL patients with HSCT-CI of ≥3, elucidating the favorable observations in elderly and comorbid CLL patients treated with bendamustine at conventional doses. 8,9 …”

Section: Discussionmentioning

confidence: 99%

“…7 Similarly, results from a phase 3 trial comparing BR with conventional fludarabine, cyclophosphamide and rituximab in CLL found the BR regimen to be better tolerated in the elderly, 8 making it the preferred choice in this patient population. 9 …”

Section: Introductionmentioning

confidence: 99%

Bendamustine added to allogeneic conditioning improves long-term outcomes in patients with CLL

Khouri

Sui

Jabbour

et al. 2016

Bone Marrow Transplant

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Bendamustine has shown a favorable safety profile when included in chemotherapy regimens for several types of lymphoma, including chronic lymphocytic leukemia (CLL). This study investigated the long-term effect of adding bendamustine to a conditioning regimen on survival, rate of engraftment, immune recovery, and graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (alloSCT) in CLL patients. These outcomes were compared to the FCR (fludarabine, cyclophosphamide, rituximab) conditioning regimen. We reviewed the data for 89 CLL patients treated on three trials at our institution. Twenty-six (29%) patients received BFR (bendamustine, fludarabine, rituximab) and 63 (71%) received FCR. Patient characteristics were similar in both groups. Ten (38%) BFR- vs. only two (3%) FCR-treated patients did not experience severe neutropenia (P = < 0.001). The 3-year overall survival estimates for the BFR and FCR groups were 82% and 51% (P = 0.03) and the 3-year progression-free survival estimates were 63% and 27% (P = 0.001). The 2-year treatment-related mortality was 8% and 23% and the incidence of grade 3 or 4 GVHD was 4% and 10%, respectively. This study is the first to report that addition of bendamustine to alloSCT conditioning for CLL patients is associated with improved survival and lower mortality, myelosuppression, and GVHD.

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Bendamustine in combination with rituximab for elderly patients with previously untreated B-cell chronic lymphocytic leukemia: A retrospective analysis of real-life practice in Italian hematology departments

Cited by 31 publications

References 21 publications

Treatment patterns, adverse events, and economic burden in a privately insured population of patients with chronic lymphocytic leukemia in the United States

Treatment patterns, adverse events, and economic burden in a privately insured population of patients with chronic lymphocytic leukemia in the United States

A phase II randomized trial comparing standard and low dose rituximab combined with alemtuzumab as initial treatment of progressive chronic lymphocytic leukemia in older patients: a trial of the ECOG‐ACRIN cancer research group (E1908)

Bendamustine added to allogeneic conditioning improves long-term outcomes in patients with CLL

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